Future Health Risk Assessment of Exposure to PM2.5 in Different Age Groups of Children in Northern Thailand

Particulate matter with a diameter less than 2.5 (PM2.5) is one of the major threats posed by air pollution to human health. It penetrates the respiratory system, particularly the lungs. In northern Thailand, the PM2.5 concentrations have significantly increased in the past decade, becoming a major concern for the health of children. This study aimed to assess the health risk of PM2.5 in different age groups of children in northern Thailand between 2020 and 2029. Based on the PM2.5 data from the simulation of the Nested Regional Climate Model with Chemistry (NRCM-Chem), the hazard quotient (HQ) was used to estimate the possible risk from PM2.5 exposure in children. In general, all age groups of children in northern Thailand will tend to experience the threat of PM2.5 in the future. In the context of age-related development periods, infants are at a higher risk than other groups (toddlers, young children, school age and adolescents), but adolescents also have a lower risk of exposure to PM2.5, albeit maintaining a high HQ value (>1). Moreover, the analysis of risk assessment in different age groups of children revealed that PM2.5 exposure might indeed affect adolescent risk differently depending on gender, with males generally at a heightened risk than females in adolescence.

data from the previous simulation [22] by the NRCM-Model to quantify the risks resulting from PM 2.5 exposure in northern Thailand. Figure 1 shows the study area in northern Thailand that is generally located in the northern peninsula of SEA and is geographically defined by many mountain ranges bordering Laos and Burma. This region has traditionally experienced air pollution driven by the burning of agriculture waste and forest fires, which release many sizes of particles over the entire year. The primary sources of air pollution in northern Thailand come from both transboundary and domestic burning [8]. Most of the air pollution in northern Thailand is caused by the burning of forests, which primarily occur in deciduous forests. Several regions in northern Thailand were forced to close in 2023 because of haze pollution. According to the Ministry of Public Health, 376,165 people were affected by air pollutionrelated health concerns, a rise of 163,491. More than 165,000 of these people suffered from respiratory issues, 80,248 from skin issues, and 70,206 from eye discomfort. The PM 2.5 concentration in February 2023 was 84.7 µg/m 3 , which exceeded the safety standards of both USEPA (35 µg/m 3 ) and the Thai (50 µg/m 3 ) guidelines, potentially leading to major health consequences (http://air4thai.com/webV3/#/Report, accessed on 20 March 2023).

Data of Future PM 2.5 Concentration
The data of future PM 2.5 used in this study was obtained from Amnuaylojaroen et al. [22]. The data were generated using the simulation of the NRCM-Chem modeling system under a climate scenario based on the representative concentration pathway (RCP8.5). The biomass-burning and anthropogenic emission inventories from RCPs were included in the simulation. When compared to the observations, the performance of the PM 2.5 dataset accurately represents the PM 2.5 pattern in northern Thailand. The statistical examination of the PM 2.5 concentrations between the modeled PM 2.5 dataset and the observation were acceptable, with an index of agreement (0.82), mean-bias (21.9), fractional error (0.043), and residue standard deviation (30.2), and an uncertainty of data with ±6.27 µg/m 3 [22]. However, the model captures the overestimation of PM 2.5 predictions. The high bias in PM 2.5 can impact the prediction of HQ values. Because the average daily dosage (ADD) that is directly related to PM 2.5 concentration was used to estimate the HQ value, a higher PM 2.5 concentration would also tend to overpredict the HQ.

Health Risk Assessment
The assessment of health risks is an essential tool for determining the possible negative consequences of pollutant exposure on human health [23][24][25]. This prediction tool examines the measurable data of exposure to assess the risk factor from pollution on human health. The exposure to humans was described by the average daily dosage (ADD),

Health Risk Assessment
The assessment of health risks is an essential tool for determining the possible negative consequences of pollutant exposure on human health [23][24][25]. This prediction tool examines the measurable data of exposure to assess the risk factor from pollution on human health. The exposure to humans was described by the average daily dosage (ADD), which was calculated as follows in Equation (1): where IR is the inhalation rate (m 3 /day); C is the pollutant concentration (µg/m 3 ); EF is the exposure frequency (days/year); ED is the exposure duration (years); ET is the exposure time (24 h/day); AT is the average exposure time (days); BW is the body weight of the children (kg). The values for these variables were derived from the previous studies, as indicated in Tables 1 and 2. Given that individuals in Asia, particularly in Thailand and China, have comparable physical circumstances, the precise values are shown in Table 1. The body weight (BW) and inhalation rate (IR) of children were used by Layton et al. [26] (Table 2), while the average time (AT) included some of the parameters used by Liang et al. [27]. The lifelong exposure of human receptors in children was calculated using an EF of 350 days per year and the hypothesis that the whole population in the research region spends no more than 14 days away from the study area [28,29]. To determine the non-carcinogenic health risks, the HQ, that is, the ratio of ADD to the reference dose (RfD), was calculated as follows in Equation The inhalation reference dose (RfD) was calculated as follows in Equation (3): where the exposure time (ET) = 24 h/day; the inhalation rate (IR) = 0.83 m 3 /h; the exposure frequency (EF) = 350 days/year; the averaging time (AT) = ED * 365 days/year; body weight (BW) = 70 kg; and ED = 30 years. RfC is the safe limit of the inhalation reference proposed by the USEPA National Ambient Air Quality Standard (NAAQS) for PM 2.5 in 2006, which is 35 µg/m 3 . The standard for safety is an HQ of 1.0. An HQ less than 1.0 denotes insignificance or "negligible risk", implying that the pollutant under consideration is unlikely to have unfavorable health consequences, even in a susceptible individual. An HQ greater than 1.0 suggests that there might be certain levels of threat to sensitive persons as a consequence of exposure [11]; however, an HQ greater than 10 implies a substantial chronic risk [30,31].

Situation of PM 2.5 Concentrations between 2020 and 2029
The daily and monthly average between 2020 and 2029 of the PM 2.5 concentration in northern Thailand is shown in Figures 2 and 3. Between 2020 and 2029, the average daily PM 2.5 concentrations will greatly surpass both the Thai (50 µg/m 3 ) and USEPA (35 µg/m 3 ) guidelines, especially during the dry season. The highest daily average PM 2.5 concentrations were at the beginning of February and ended in April with ranges of 40-400 µg/m 3 in the future ( Figure 2) while the PM 2.5 concentrations dropped in the rainy season (May to October) and peaked in the dry season (November to December and January to April) (2020-2029) ( Figure 3). The worst PM 2.5 values were detected predominantly between February and March. In northern Thailand, biomass burning emissions govern the seasonal variance of PM 2.5 [8,22]. PM 2.5 is extensively distributed by biomass burning including open and waste burning, in advance of the forthcoming rain and rice seeding during the dry season [8]. open and waste burning, in advance of the forthcoming rain and rice seeding during the dry season [8].

Hazard Quote in Different Age Groups of Children in Northern Thailand between 2020 and 2029
In this study, the values of HQ were estimated for children in order to evaluate the

Hazard Quote in Different Age Groups of Children in Northern Thailand between 2020 and 2029
In this study, the values of HQ were estimated for children in order to evaluate the non-carcinogenic threat of PM 2.5 in northern Thailand. Figure 3a depicts the daily averages of the HQ associated with PM 2.5 in northern Thailand throughout the age-related development period of 2020-2029. Militaru and Martinovici [32] classified the age-related development phase. Infants were 1 month to 1 year old, toddlers were 1 to 3 years old, young children were 3 to 6 years old, school-age children were 6 to 12 years old, and adolescents were 12 to 18 years old. During January and April, the daily mean of the HQ was greater than 1. The highest HQ value was discovered in March, suggesting that all age groups of children in northern Thailand face significant danger in the near future. When comparing the age-related development periods, infants had a larger risk than other groups, with an HQ value of 23.96, whereas adolescents had a decreased risk of exposure to PM 2.5 , although the HQ value remained quite high (10.28 for adolescents). Figure 3b depicts the monthly averages of the HQ associated with PM 2.5 in different age groups of children in northern Thailand between 2020 and 2029. From February through April, the monthly averages of the HQ values were larger than one, suggesting a high risk for all children in northern Thailand. In March, the highest HQ value was discovered in a group of infants. In the dry season, the HQ values between February and April were higher than during November and January. This is likely due to the emissions from the massive biomass burnings from agricultural and waste burning in preparation for the rice planting season. Along with the long-range transport of air pollutants from neighboring countries such as Laos, Vietnam, and Burma, which is induced by meteorological conditions, these factors contribute to the high air pollution in northern Thailand [8].

Discussion
The results of this study indicate that the HQ values of infants were acutely high-risk and higher in comparison to the other groups. This is most likely due to a mix of behavior, environment, and physical factors. They are highly susceptible to the developing fetus and the early years of their lives, when their respiratory systems, organ systems, and brains are still growing. It is uncertain what biological processes induce PM 2.5 inhalation to cause infant death. Nevertheless, Brook et al. [33] reported that PM 2.5 exposure likely promotes oxidative stress, systemic inflammation, and blood clotting. As a result, Kannan et al. [34] explained that if a pregnant woman becomes exposed to PM 2.5 , a chain reaction of unfavorable biological reactions may endanger the health of the fetus. Previous studies by Feng et al. [31], and Valentino et al. [35] discovered that PM exposure changed the placental function and structure, potentially impairing fetal development and growth. Simultaneously, Wick et al. [36] revealed that PM 2.5 was able to pass the cell membrane. As a result, fine particulates that penetrate directly through the placenta would impair the fetus because the immune system of the fetus is still developing [37]. Prenatal exposure to a toxic drug can disrupt the development of many systems necessary for life. For instance, prenatal PM 2.5 exposure may hinder the development of the cardiovascular and central nervous systems [38]. Furthermore, prenatal PM 2.5 exposure may disrupt lung maturation by interacting with lung growth, neurogenesis, and differentiation [39]. Prenatal exposure to PM 2.5 might well be associated with infant mortality, provided that disruptions in the formation and function of biological systems before birth are associated with negative health consequences later in life. Due to the role of exposure time on fetal susceptibility, the magnitude of the adverse effects of PM 2.5 can fluctuate during the perinatal period [40]. With regard to cognitive function, PM 2.5 exposure during earlier stages of pregnancy may be associated with severe issues, whereas exposure during the later stages of pregnancy may be associated with inadequacies [38].
Particulate matter is likely to be associated with gender [41]. Due to differences in respiratory symptom rates of growth, disentangling the role of gender in particle pollution connections in children may be more difficult [42]. It has been postulated that observed disparities in poor air quality consequences between males and females were caused by sexrelated biological factors such as hormone balancing and body structure or sex differences in behavior patterns, doses, or the accuracy of measurements [43]. Furthermore, because males have a greater death rate than females, the lag in fetal respiratory system development in males might explain their high susceptibility to PM 2.5 exposure [44,45]. Moreover, long-term prenatal PM 2.5 exposure disrupts the Ras homolog gene family member A (RhoA) pathway in males [46]. Since the enhanced production of reactive oxygen species is a putative stimulation process of the RhoA system for PM 2.5 , males might be more prone to heart disease when exposed to PM 2.5 [46,47]. Furthermore, some studies have found that male and female lungs respond differently to air pollution exposure [48][49][50][51]. This likely occurred because male and female lungs differed earlier in fetal and maternal growth all through their lives, with female lungs maturing earlier in terms of surfactant production [52,53]. Women have smaller lungs than men throughout their lives, but their respiratory anatomy is more beneficial, with a larger airway size in comparison to the amount of pulmonary parenchyma. As a result, airway hyperreactivity and asthma are more prevalent in boys than in girls during childhood.
Furthermore, PM 2.5 does not only have a non-carcinogenic risk on human health; its chemical composition also has an effect on carcinogenic risk on human health. The latest studies demonstrate that the composition of particulate matter is related to human health. For example, Phairuang et al. [54,55] investigated the health risk of PM 0.1 and its trace elements such as aluminum (Al), barium (Ba), potassium (K), iron (Fe), chromium (Cr), copper (Cu), nickel (Ni), sodium (Na), manganese (Mn), magnesium (Mg), titanium (Ti), lead (Pb), and zinc (Zn) on humans in Bangkok and Hat Yai, Thailand. They discovered that biomass burning was the predominant source of PM and had a high risk for human health in those areas. Additionally, Insian et al. [56] evaluated the respiratory health risk posed by size-fractionated PM-bound polycyclic aromatic hydrocarbons (PAHs) in urban and rural Chiang Mai, northern Thailand. They discovered a rather high respiratory health risk during the smoky haze season in Chiang Mai, Thailand based on toxicity equivalent concentrations of the PAH-bound size-fractionated particulate matters (SPMs) and inhalation cancer risk (ICR). Wang et al. [57] revealed that the health risk assessment of heavy metals showed that non-carcinogenic hazards are not expected to occur, while Cr contributed the highest cancer risk in the industrial areas of China.

Conclusions
The purpose of this study was to examine health risks among different age groups of children in northern Thailand between 2020 and 2029. The analysis of PM 2.5 concentrations in the future found that they tended to exceed both the USEPA and Thai guidelines, mainly in the dry season. The air quality in the wet season is expected to be better than the dry season, when PM 2.5 concentrations tend to be lower. The highest future PM 2.5 concentrations were detected in ranges of 40 to 400 µg/m 3 in the dry season, especially in February and March. As a result, the highest concentration of PM 2.5 was found in March. At the same time, the highest average of HQ values was found with 13.89, 12.27, 10.82, 8.91, and 5.96 for infants, toddlers, young children, school age, and adolescents, respectively, while the HQ of different age groups of children showed the highest value in March with 13.89, 12.27, 10.82, and 9.02 for children aged less than 1 year, 1 to 2 years, 3 to 5 years, and 6 to 8 years, respectively. Meanwhile, the HQ of children aged 9 to 11 years, 12 to 14 years, and 15 to 18 years was in the range of 6.04 to 9.12 for males and 5.03 to 8.47 for females. In conclusion, in general, children of all ages are likely to suffer from PM 2.5 in the future. Infants are especially at higher risk than other groups of children. Simultaneously, adolescent males tend to be at higher risk than females.  Data Availability Statement: All data generated or analyzed during this study are included in this published article.